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1.
FASEB J ; 38(4): e23480, 2024 Feb 29.
Artigo em Inglês | MEDLINE | ID: mdl-38354025

RESUMO

Accumulating evidence suggests that dysregulation of FOXO3a plays a significant role in the progression of various malignancies, including hepatocellular carcinoma (HCC). FOXO3a inactivation, driven by oncogenic stimuli, can lead to abnormal cell growth, suppression of apoptosis, and resistance to anticancer drugs. Therefore, FOXO3a emerges as a potential molecular target for the development of innovative treatments in the era of oncology. Linagliptin (LNGTN), a DPP-4 inhibitor known for its safe profile, has exhibited noteworthy anti-inflammatory and anti-oxidative properties in previous in vivo studies. Several potential molecular mechanisms have been proposed to explain these effects. However, the capacity of LNGTN to activate FOXO3a through AMPK activation has not been investigated. In our investigation, we examined the potential repurposing of LNGTN as a hepatoprotective agent against diethylnitrosamine (DENA) intoxication. Additionally, we assessed LNGTN's impact on apoptosis and autophagy. Following a 10-week administration of DENA, the liver underwent damage marked by inflammation and early neoplastic alterations. Our study presents the first experimental evidence demonstrating that LNGTN can reinstate the aberrantly regulated FOXO3a activity by elevating the nuclear fraction of FOXO3a in comparison to the cytosolic fraction, subsequent to AMPK activation. Moreover, noteworthy inactivation of NFκB induced by LNGTN was observed. These effects culminated in the initiation of apoptosis, the activation of autophagy, and the manifestation of anti-inflammatory, antiproliferative, and antiangiogenic outcomes. These effects were concomitant with improved liver function and microstructure. In conclusion, our findings open new avenues for the development of novel therapeutic strategies targeting the AMPK/FOXO3a signaling pathway in the management of chronic liver damage.


Assuntos
Carcinoma Hepatocelular , Inibidores da Dipeptidil Peptidase IV , Neoplasias Hepáticas , Animais , Ratos , Linagliptina/farmacologia , Proteínas Quinases Ativadas por AMP , Dietilnitrosamina/toxicidade , Carcinoma Hepatocelular/induzido quimicamente , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/induzido quimicamente , Neoplasias Hepáticas/tratamento farmacológico , Hipoglicemiantes , Inibidores de Proteases , Antivirais , Anti-Inflamatórios
2.
Eur J Pharm Biopharm ; 196: 114205, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38311187

RESUMO

The targeting and mucoadhesive features of chitosan (CS)-linked solid lipid nanoparticles (SLNs) were exploited to efficiently deliver fexofenadine (FEX) into the colon, forming a novel and potential oral therapeutic option for ulcerative colitis (UC) treatment. Different FEX-CS-SLNs with varied molecular weights of CS were prepared and optimized. Optimized FEX-CS-SLNs exhibited 229 ± 6.08 nm nanometric size, 36.3 ± 3.18 mV zeta potential, 64.9 % EE, and a controlled release profile. FTIR, DSC, and TEM confirmed good drug entrapment and spherical particles. Mucoadhesive properties of FEX-CS-SLNs were investigated through mucin incubation and exhibited considerable mucoadhesion. The protective effect of FEX-pure, FEX-market, and FEX-CS-SLNs against acetic acid-induced ulcerative colitis in rats was examined. Oral administration of FEX-CS-SLNs for 14 days before ulcerative colitis induction reversed UC symptoms and almost restored the intestinal mucosa to normal integrity and inhibited Phosphatidylinositol-3 kinase (73.6 %), protein kinase B (73.28 %), and elevated nuclear factor erythroid 2-related factor 2 (185.9 %) in colonic tissue. Additionally, FEX-CS-SLNs inhibited tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) to (70.79 % & 72.99 %) in colonic tissue. The ameliorative potential of FEX-CS-SLNs outperformed that of FEX-pure and FEX-market. The exceptional protective effect of FEX-CS-SLNs makes it a potentially effective oral system for managing ulcerative colitis.


Assuntos
Quitosana , Colite Ulcerativa , Lipossomos , Nanopartículas , Terfenadina/análogos & derivados , Ratos , Animais , Colite Ulcerativa/tratamento farmacológico , Portadores de Fármacos/efeitos adversos , Tamanho da Partícula
3.
Naunyn Schmiedebergs Arch Pharmacol ; 397(4): 1957-1969, 2024 04.
Artigo em Inglês | MEDLINE | ID: mdl-37801146

RESUMO

Pheochromocytoma (PCC) is a neuroendocrine tumor that produces and secretes catecholamine from either the adrenal medulla or extra-adrenal locations. MicroRNAs (miRNAs, miR) can be used as biomarkers to detect cancer or the return of a previously treated disease. Blood-borne miRNAs might be envisioned as noninvasive markers of malignancy or prognosis, and new studies demonstrate that microRNAs are released in body fluids as well as tissues. MiRNAs have the potential to be therapeutic targets, which would greatly increase the restricted therapy options for adrenal tumors. This article aims to consolidate and synthesize the most recent studies on miRNAs in PCC, discussing their potential clinical utility as diagnostic and prognostic biomarkers while also addressing their limitations.


Assuntos
Neoplasias das Glândulas Suprarrenais , MicroRNAs , Feocromocitoma , Humanos , Feocromocitoma/diagnóstico , Feocromocitoma/genética , Feocromocitoma/patologia , Neoplasias das Glândulas Suprarrenais/diagnóstico , Neoplasias das Glândulas Suprarrenais/genética , Neoplasias das Glândulas Suprarrenais/patologia , Prognóstico , Biomarcadores Tumorais , Regulação Neoplásica da Expressão Gênica
4.
Pathol Res Pract ; 252: 154947, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37977032

RESUMO

Malignant pleural mesothelioma (MPM) is a highly invasive form of lung cancer that adversely affects the pleural and other linings of the lungs. MPM is a very aggressive tumor that often has an advanced stage at diagnosis and a bad prognosis (between 7 and 12 months). When people who have been exposed to asbestos experience pleural effusion and pain that is not explained, MPM should be suspected. After being diagnosed, most MPM patients have a one- to four-year life expectancy. The life expectancy is approximately six months without treatment. Despite the plethora of current molecular investigations, a definitive universal molecular signature has yet to be discovered as the causative factor for the pathogenesis of MPM. MicroRNAs (miRNAs) are known to play a crucial role in the regulation of gene expression at the posttranscriptional level. The association between the expression of these short, non-coding RNAs and several neoplasms, including MPM, has been observed. Although the incidence of MPM is very low, there has been a significant increase in research focused on miRNAs in the past few years. In addition, miRNAs have been found to have a role in various regulatory signaling pathways associated with MPM, such as the Notch signaling network, Wnt/ß-catenin, mutation of KRAS, JAK/STAT signaling circuit, protein kinase B (AKT), and Hedgehog signaling pathway. This study provides a comprehensive overview of the existing understanding of the roles of miRNAs in the underlying mechanisms of pathogenic symptoms in MPM, highlighting their potential as viable targets for therapeutic interventions.


Assuntos
Neoplasias Pulmonares , Mesotelioma Maligno , Mesotelioma , MicroRNAs , Neoplasias Pleurais , Humanos , MicroRNAs/genética , Mesotelioma/diagnóstico , Neoplasias Pleurais/patologia , Proteínas Hedgehog , Neoplasias Pulmonares/patologia , Transdução de Sinais/genética
5.
Pathol Res Pract ; 252: 154949, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37992507

RESUMO

Oral cancer (OC) is the predominant type originating in the head and neck region. The incidence of OC is mostly associated with behavioral risk factors, including tobacco smoking and excessive alcohol intake. Additionally, there is a lower but still significant association with viral infections such as human papillomaviruses and Epstein-Barr viruses. Furthermore, it has been observed that heritable genetic variables are linked to the risk of OC, in addition to the previously mentioned acquired risk factors. The current absence of biomarkers for OC diagnosis contributes to the frequent occurrence of advanced-stage diagnoses among patients. Non-coding RNAs (ncRNAs), including microRNAs (miRNAs), long non-coding RNAs, and circular RNAs, have been observed to exert a significant effect on the transcriptional control of target genes involved in cancer, either through direct or indirect mechanisms. miRNAs are a class of short ncRNAs that play a role in regulating gene expression by enabling mRNA degradation or translational repression at the post-transcriptional phase. miRNAs are known to play a fundamental role in the development of cancer and the regulation of oncogenic cell processes. Notch signaling, PTEN/Akt/mTOR axis, KRAS mutation, JAK/STAT signaling, P53, EGFR, and the VEGFs have all been linked to OC, and miRNAs have been shown to have a role in all of these. The dysregulation of miRNA has been identified in cases of OC and is linked with prognosis.


Assuntos
MicroRNAs , Neoplasias Bucais , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias Bucais/genética , Neoplasias Bucais/diagnóstico , Transdução de Sinais/genética , Regulação da Expressão Gênica , Herpesvirus Humano 4/genética , Regulação Neoplásica da Expressão Gênica
6.
Pathol Res Pract ; 251: 154856, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37806171

RESUMO

Pheochromocytoma (PCC) is a type of neuroendocrine tumor that originates from adrenal medulla or extra-adrenal chromaffin cells and results in the production of catecholamine. Paroxysmal hypertension and cardiovascular crises were among the clinical signs experienced by people with PCC. Five-year survival of advanced-stage PCC is just around 40% despite the identification of various molecular-level fundamentals implicated in these pathogenic pathways. MicroRNAs (miRNAs, miRs) are a type of short, non-coding RNA (ncRNA) that attach to the 3'-UTR of a target mRNA, causing translational inhibition or mRNA degradation. Evidence is mounting that miRNA dysregulation plays a role in the development, progression, and treatment of cancers like PCC. Hence, this study employs a comprehensive and expedited survey to elucidate the potential role of miRNAs in the development of PCC, surpassing their association with survival rates and treatment options in this particular malignancy.


Assuntos
Neoplasias das Glândulas Suprarrenais , MicroRNAs , Feocromocitoma , Humanos , Feocromocitoma/diagnóstico , MicroRNAs/genética , Neoplasias das Glândulas Suprarrenais/genética , Neoplasias das Glândulas Suprarrenais/diagnóstico , Catecolaminas , Transdução de Sinais
7.
Pathol Res Pract ; 250: 154817, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37713736

RESUMO

Malignant pleural mesothelioma (MPM) is a highly lethal form of pleural cancer characterized by a scarcity of effective therapeutic interventions, resulting in unfavorable prognoses for afflicted individuals. Besides, many patients experience substantial consequences from being diagnosed in advanced stages. The available diagnostic, prognostic, and therapeutic options for MPM are restricted in scope. MicroRNAs (miRNAs) are a subset of small, noncoding RNA molecules that exert significant regulatory influence over several cellular processes within cell biology. A wide range of miRNAs have atypical expression patterns in cancer, serving specific functions as either tumor suppressors or oncomiRs. This review aims to collate, epitomize, and analyze the latest scholarly investigations on miRNAs that are believed to be implicated in the dysregulation leading to MPM. miRNAs are also discussed concerning their potential clinical usefulness as diagnostic and prognostic biomarkers for MPM. The future holds promising prospects for enhancing diagnostic, prognostic, and therapeutic modalities for MPM, with miRNAs emerging as a potential trigger for such advancements.

8.
Pathol Res Pract ; 249: 154771, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37611429

RESUMO

Merkel cell carcinoma (MCC) is an uncommon invasive form of skin cancer that typically manifests as a nodule on the face, head, or neck that is flesh-colored or bluish-red in appearance. Rapid growth and metastasis are hallmarks of MCC. MCC has the second-greatest mortality rate among skin cancers after melanoma. Despite the recent cascade of molecular investigations, no universal molecular signature has been identified as responsible for MCC's pathogenesis. The microRNAs (miRNAs) play a critical role in the post-transcriptional regulation of gene expression. Variations in the expression of these short, non-coding RNAs have been associated with various malignancies, including MCC. Although the incidence of MCC is very low, a significant amount of study has focused on the interaction of miRNAs in MCC. As such, the current survey is a speedy intensive route revealing the potential involvement of miRNAs in the pathogenesis of MCC beyond their association with survival in MCC.


Assuntos
Carcinoma de Célula de Merkel , Melanoma , MicroRNAs , Neoplasias Cutâneas , Humanos , MicroRNAs/genética , Carcinoma de Célula de Merkel/genética , Transdução de Sinais , Neoplasias Cutâneas/genética , Melanoma/genética
9.
Molecules ; 28(15)2023 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-37570781

RESUMO

In the current study, clove oil nanoemulsion (CL-nanoemulsion) and emulsion (CL-emulsion) were prepared through an ecofriendly method. The prepared CL-nanoemulsion and CL-emulsion were characterized using dynamic light scattering (DLS) and a transmission electron microscope (TEM), where results illustrated that CL-nanoemulsion droplets were approximately 32.67 nm in size and spherical in shape, while CL-nanoemulsion droplets were approximately 225.8 nm with a spherical shape. The antibacterial activity of CL-nanoemulsion and CL-emulsion was carried out using a microbroth dilution method. Results revealed that the preferred CL-nanoemulsion had minimal MIC values between 0.31 and 5 mg/mL. The antibiofilm efficacy of CL-nanoemulsion against S. aureus significantly decreased the development of biofilm compared with CL-emulsion. Furthermore, results illustrated that CL-nanoemulsion showed antifungal activity significantly higher than CL-emulsion. Moreover, the prepared CL-nanoemulsion exhibited outstanding antifungal efficiency toward Candida albicans, Cryptococcus neoformans, Aspergillus brasiliensis, A. flavus, and A. fumigatus where MICs were 12.5, 3.12, 0.78, 1.56, and 1.56 mg/mL, respectively. Additionally, the prepared CL-nanoemulsion was analyzed for its antineoplastic effects through a modified MTT assay for evaluating apoptotic and cytotoxic effects using HepG2 and MCF-7 cell lines. MCF-7 breast cancer cells showed the lowest IC50 values (3.4-fold) in CL-nanoemulsion relative to that of CL-emulsion. Thus, CL-nanoemulsion induces apoptosis in breast cancer cells by inducing caspase-8 and -9 activity and suppressing VEGFR-2. In conclusion, the prepared CL-nanoemulsion had antibacterial, antifungal, and antibiofilm as well as anticancer properties, which can be used in different biomedical applications after extensive studies in vivo.


Assuntos
Antibacterianos , Antifúngicos , Antineoplásicos , Biofilmes , Óleos Voláteis , Syzygium , Biofilmes/efeitos dos fármacos , Antineoplásicos/química , Antineoplásicos/farmacologia , Óleos Voláteis/química , Óleos Voláteis/farmacologia , Emulsões , Syzygium/química , Difusão Dinâmica da Luz , Microscopia Eletrônica de Transmissão , Células Hep G2 , Células MCF-7 , Humanos , Apoptose , Antibacterianos/química , Antibacterianos/farmacologia , Antifúngicos/química , Antifúngicos/farmacologia , Sistemas de Liberação de Fármacos por Nanopartículas , Nanoestruturas/química , Staphylococcus aureus/efeitos dos fármacos , Fungos/efeitos dos fármacos
10.
Pathol Res Pract ; 248: 154690, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37473498

RESUMO

Adrenocortical carcinoma (ACC) is a highly malignant infrequent tumor with a dismal prognosis. microRNAs (miRNAs, miRs) are crucial in post-transcriptional gene expression regulation. Due to their ability to regulate multiple gene networks, miRNAs are central to the hallmarks of cancer, including sustained proliferative signaling, evasion of growth suppressors, resistance to cell death, replicative immortality, induction/access to the vasculature, activation of invasion and metastasis, reprogramming of cellular metabolism, and avoidance of immune destruction. ACC represents a singular form of neoplasia associated with aberrations in the expression of evolutionarily conserved short, non-coding RNAs. Recently, the role of miRNAs in ACC has been examined extensively despite the disease's rarity. Hence, the current review is a fast-intensive track elucidating the potential role of miRNAs in the pathogenesis of ACC besides their association with the survival of ACC.


Assuntos
Neoplasias do Córtex Suprarrenal , Carcinoma Adrenocortical , MicroRNAs , Humanos , Carcinoma Adrenocortical/genética , Carcinoma Adrenocortical/patologia , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias do Córtex Suprarrenal/genética , Neoplasias do Córtex Suprarrenal/patologia , Prognóstico , Transdução de Sinais/genética
11.
Int J Pharm ; 643: 123224, 2023 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-37451327

RESUMO

Rheumatoid arthritis (RA), a distressing inflammatory autoimmune disease, is managed mainly by Disease-modifying antirheumatic drugs (DMARDs), e.g. leflunomide (LEF). LEF (BCS class II) has limited solubility and adverse effects following its systemic exposure. The appealing antirheumatic properties of both clove oil and chitosan (CS) were exploited to design oral leflunomide (LEF)-loaded nanoemulsion (NE) system to augment the therapeutic action of LEF and decrease its systemic side effects as well. Different LEF-NEs were prepared using clove oil, Tween® 20 (surfactant), and PEG 400(co-surfactant) and characterized by thermodynamic stability, percentage transmittance, cloud point, size analysis, and drug content. Optimized LEF-NE was subjected to CS coating forming LEF-CS-NE that exhibited nanometric size range, prolonged drug release, and good physical stability. In vivo anti-rheumatic activity of pure LEF, market LEF, and LEF-CS-NE was assessed utilizing a complete Freund's adjuvant (CFA) rat model. Treatment with LEF-CS-NE reduced edema rate (48.68% inhibition) and caused a marked reduction in interleukin-6 (IL-6) (510.9 ± 2.48 pg/ml), tumor necrosis factor- α (TNF-α) (397.3 ± 2.53 pg/ml), and rheumatoid factor (RF) (42.58 ± 0.49 U/ml). Furthermore, LEF-CS-NE reduced serum levels of glutamic pyruvic transaminase (GPT) to (83.19%) and glutamic oxaloacetic transaminase (GOT) to (40.68%) compared to the control + ve group. The effects of LEF-CS-NE were also superior to both pure and market LEF and showed better results in histopathological studies of paws, liver, kidney, lung, and heart. The remarkable therapeutic and safety profile of LEF-CS-NE makes it a potential oral system for the management of RA.


Assuntos
Antirreumáticos , Artrite Reumatoide , Quitosana , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos , Ratos , Animais , Leflunomida , Quitosana/uso terapêutico , Óleo de Cravo , Metotrexato , Artrite Reumatoide/tratamento farmacológico , Fator de Necrose Tumoral alfa , Efeitos Colaterais e Reações Adversas Relacionados a Medicamentos/tratamento farmacológico , Tensoativos
12.
Pathol Res Pract ; 248: 154704, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37499518

RESUMO

Multiple myeloma (MM) is a tumor of transformed plasma cells. It's the second most common hematologic cancer after non-Hodgkin lymphoma. MM is a complex disease with many different risk factors, including ethnicity, race, and epigenetics. The microRNAs (miRNAs) are a critical epigenetic factor in multiple myeloma, influencing key aspects such as pathogenesis, prognosis, and resistance to treatment. They have the potential to assist in disease diagnosis and modulate the resistance behavior of MM towards therapeutic regimens. These characteristics could be attributed to the modulatory effects of miRNAs on some vital pathways such as NF-KB, PI3k/AKT, and P53. This review discusses the role of miRNAs in MM with a focus on their role in disease progression, diagnosis, and therapeutic resistance.


Assuntos
MicroRNAs , Mieloma Múltiplo , Humanos , MicroRNAs/metabolismo , Mieloma Múltiplo/diagnóstico , Mieloma Múltiplo/tratamento farmacológico , Mieloma Múltiplo/genética , Fosfatidilinositol 3-Quinases/metabolismo , Resistencia a Medicamentos Antineoplásicos/genética , Prognóstico , Regulação Neoplásica da Expressão Gênica
13.
Pathol Res Pract ; 248: 154665, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37418996

RESUMO

Adrenocortical carcinoma (ACC) is an uncommon aggressive endocrine malignancy that is nonetheless associated with significant mortality and morbidity rates because of endocrine and oncological consequences. Recent genome-wide investigations of ACC have advanced our understanding of the disease, but substantial obstacles remain to overcome regarding diagnosis and prognosis. MicroRNAs (miRNAs, miRs) play a crucial role in the development and metastasis of a wide range of carcinomas by regulating the expression of their target genes through various mechanisms causing translational repression or messenger RNA (mRNA) degradation. Along with miRNAs in the adrenocortical cancerous tissue, circulating miRNAs are considered barely invasive diagnostic or prognostic biomarkers of ACC. miRNAs may serve as treatment targets that expand the rather-limited therapeutic repertoire in the field of ACC. Patients with advanced ACC still have a poor prognosis when using the available treatments, despite a substantial improvement in understanding of the illness over the previous few decades. Accordingly, in this review, we provide a crucial overview of the recent studies in ACC-associated miRNAs regarding their diagnostic, prognostic, and potential therapeutic relevance.


Assuntos
Neoplasias do Córtex Suprarrenal , Carcinoma Adrenocortical , MicroRNAs , Humanos , Carcinoma Adrenocortical/diagnóstico , Carcinoma Adrenocortical/genética , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias do Córtex Suprarrenal/diagnóstico , Neoplasias do Córtex Suprarrenal/genética , Prognóstico , Resistência a Medicamentos
14.
Pathol Res Pract ; 248: 154715, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37517169

RESUMO

Multiple myeloma (MM) is a cancer of plasma cells that has been extensively studied in recent years, with researchers increasingly focusing on the role of microRNAs (miRNAs) in regulating gene expression in MM. Several non-coding RNAs have been demonstrated to regulate MM pathogenesis signaling pathways. These pathways might regulate MM development, apoptosis, progression, and therapeutic outcomes. They are Wnt/ß-catenin, PI3K/Akt/mTOR, P53 and KRAS. This review highlights the impending role of miRNAs in MM signaling and their relationship with MM therapeutic interventions.

15.
Pathol Res Pract ; 248: 154684, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37454489

RESUMO

Gallbladder cancer (GBC) is characterized by a highly invasive nature and a poor prognosis, with adenocarcinoma being the main histological subtype. According to statistical data, patients diagnosed with advanced GBC have a survival rate of less than 5% for 5 years. Despite the novel therapeutic techniques, the unsatisfactory results could be related to the underlying biology of tumor cells and resistance to chemotherapy. Early diagnosis is more important than clinical therapy as it assists in determining the pathological stage of cancer and facilitates the selection of appropriate medication. Hence, it is very important to understand the precise pathogenesis of GBC and to discover potential novel biomarkers for early diagnosis of GBC. Non-coding RNAs, such as microRNAs, long non-coding RNAs, and circular RNAs, have been found to influence the transcriptional regulation of target genes associated with cancer, either directly or indirectly. microRNAs are a group of small, non-coding, single-stranded RNAs that are expressed endogenously. miRNAs play significant roles in various fundamental cellular processes. Therefore, miRNAs have the potential to serve as valuable biomarkers and therapeutic targets for GBC.


Assuntos
Carcinoma in Situ , Neoplasias da Vesícula Biliar , MicroRNAs , Humanos , MicroRNAs/genética , Neoplasias da Vesícula Biliar/diagnóstico , Neoplasias da Vesícula Biliar/genética , Neoplasias da Vesícula Biliar/patologia , Regulação Neoplásica da Expressão Gênica/genética , Resistência a Medicamentos , Prognóstico
16.
Pathol Res Pract ; 248: 154611, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37315401

RESUMO

Testicular germ cell tumors (TGCTs) are the most common testicular neoplasms in adolescents and young males. Understanding the genetic basis of TGCTs represents a growing need to cope with the increased incidence of these neoplasms. Although the cure rates have been comparatively increased, investigation of mechanisms underlying the incidence, progression, metastasis, recurrence, and therapy resistance is still necessary. Early diagnosis and non-compulsory clinical therapeutic agents without long-term side effects are now required to reduce the cancer burden, especially in the younger age groups. MicroRNAs (miRNAs) control an extensive range of cellular functions and exhibit a pivotal action in the development and spreading of TGCTs. Because of their dysregulation and disruption in function, miRNAs have been linked to the malignant pathophysiology of TGCTs by influencing many cellular functions involved in the disease. These biological processes include increased invasive and proliferative perspective, cell cycle dysregulation, apoptosis disruption, stimulation of angiogenesis, epithelial-mesenchymal transition (EMT) and metastasis, and resistance to certain treatments. Herein, we present an up-to-date review of the biogenesis of miRNAs, miRNA regulatory mechanisms, clinical challenges, and therapeutic interventions of TGCTs, and role of nanoparticles in the treatment of TGCTs.


Assuntos
MicroRNAs , Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Masculino , Adolescente , Humanos , MicroRNAs/genética , MicroRNAs/uso terapêutico , Neoplasias Embrionárias de Células Germinativas/genética , Neoplasias Testiculares/genética , Neoplasias Testiculares/patologia , Transdução de Sinais/genética
17.
Pathol Res Pract ; 248: 154590, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37295259

RESUMO

Cancer of the salivary glands is one of the five major types of head and neck cancer. Due to radioresistance and a strong propensity for metastasis, the survival rate for nonresectable malignant tumors is dismal. Hence, more research is needed on salivary cancer's pathophysiology, particularly at the molecular level. The microRNAs (miRNAs) are a type of noncoding RNA that controls as many as 30% of all genes that code for proteins at the posttranscriptional level. Signature miRNA expression profiles have been established in several cancer types, suggesting a role for miRNAs in the incidence and progression of human malignancies. Salivary cancer tissues were shown to have significantly aberrant levels of miRNAs compared to normal salivary gland tissues, supporting the hypothesis that miRNAs play a crucial role in the carcinogenesis of salivary gland cancer (SGC). Besides, several SGC research articles reported potential biomarkers and therapeutic targets for the miRNA-based treatment of this malignancy. In this review, we will explore the regulatory impact of miRNAs on the processes underlying the molecular pathology of SGC and provide an up-to-date summary of the literature on miRNAs that impacted this malignancy. We will eventually share information about their possible use as diagnostic, prognostic, and therapeutic biomarkers in SGC.


Assuntos
Neoplasias de Cabeça e Pescoço , MicroRNAs , Neoplasias das Glândulas Salivares , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Neoplasias das Glândulas Salivares/diagnóstico , Neoplasias das Glândulas Salivares/genética , Neoplasias das Glândulas Salivares/metabolismo , Glândulas Salivares/patologia , Neoplasias de Cabeça e Pescoço/patologia , Resistência a Medicamentos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Regulação Neoplásica da Expressão Gênica/genética
18.
Pathol Res Pract ; 248: 154612, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37327566

RESUMO

Testicular cancer (TC) is one of the most frequently incident solid tumors in males. A growing prevalence has been documented in developed countries. Although recent advances have made TC an exceedingly treatable cancer, numerous zones in TC care still have divisive treatment decisions. In addition to physical examination and imaging techniques, conventional serum tumor markers have been traditionally used for the diagnosis of testicular germ cell tumors (TGCT). Unlike other genital and urinary tract tumors, recent research methods have not been broadly used in TGCTs. Even though several challenges in TC care must be addressed, a dedicated group of biomarkers could be particularly beneficial to help classify patient risk, detect relapse early, guide surgery decisions, and tailor follow-up. Existing tumor markers (Alpha-fetoprotein, human chorionic gonadotrophin, and lactate dehydrogenase) have limited accuracy and sensitivity when used as diagnostic, prognostic, or predictive markers. At present, microRNAs (miRNA or miR) play a crucial role in the process of several malignancies. The miRNAs exhibit pronounced potential as novel biomarkers since they reveal high stability in body fluids, are easily detected, and are relatively inexpensive in quantitative assays. In this review, we aimed to shed light on the recent novelties in developing microRNAs as diagnostic and prognostic markers in TC and discuss their clinical applications in TC management.


Assuntos
MicroRNAs , Neoplasias Embrionárias de Células Germinativas , Neoplasias Testiculares , Masculino , Humanos , MicroRNAs/genética , Neoplasias Testiculares/diagnóstico , Neoplasias Testiculares/genética , Neoplasias Testiculares/patologia , Neoplasias Embrionárias de Células Germinativas/diagnóstico , Neoplasias Embrionárias de Células Germinativas/genética , Biomarcadores Tumorais/genética , Resistência a Medicamentos
19.
Pathol Res Pract ; 246: 154529, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37196470

RESUMO

Globally, esophageal cancer (EC) is the 6th leading cause of cancer-related deaths and the second deadliest gastrointestinal cancer. Multiple genetic and epigenetic factors, such as microRNAs (miRNAs), influence its onset and progression. miRNAs are short nucleic acid molecules that can regulate multiple cellular processes by regulating gene expression. Therefore, EC initiation, progression, apoptosis evasions, invasion capacity, promotion, angiogenesis, and epithelial-mesenchymal transition (EMT) enhancement are associated with miRNA expression dysregulation. Wnt/-catenin signaling, Mammalian target of rapamycin (mTOR)/P-gp, phosphoinositide-3-kinase (PI3K)/AKT/c-Myc, epidermal growth factor receptor (EGFR), and transforming growth factor (TGF)-ß signaling are crucial pathways in EC that are controlled by miRNAs. This review was conducted to provide an up-to-date assessment of the role of microRNAs in EC pathogenesis and their modulatory effects on responses to various EC treatment modalities.


Assuntos
Neoplasias Esofágicas , MicroRNAs , Humanos , MicroRNAs/genética , Neoplasias Esofágicas/patologia , Via de Sinalização Wnt/genética , Fator de Crescimento Transformador beta/metabolismo , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica
20.
Pharm Biol ; 60(1): 2134-2144, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36305518

RESUMO

CONTEXT: Chitosan is a biocompatible polysaccharide that has been widely exploited in biomedical and drug delivery applications. OBJECTIVE: This study explores the renoprotective effect of chitosan nanoparticles in vivo in rats. MATERIALS AND METHODS: Chitosan nanoparticles were prepared via ionotropic gelation method, and several in vitro characterizations were performed, including measurements of particle size, zeta potential, polydispersity index, Fourier transform-infrared spectroscopy, differential scanning calorimetry, and transmission electron microscopy (TEM) imaging. Wistar rats were divided randomly into four groups; negative control, CCl4-induced nephrotoxicity (untreated), and two groups receiving CCl4 + chitosan NPs (10 and 20 mg/kg) orally for 2 weeks. The renoprotective effect was assessed by measuring oxidative, apoptotic, and inflammatory biomarkers, and via histopathological and immunohistochemical examinations for the visualization of NF-κB and COX-2 in renal tissues. RESULTS: Monodisperse spherical nanosized (56 nm) particles were successfully prepared as evidenced by dynamic light scattering and TEM. Oral administration of chitosan nanoparticles (10 and 20 mg/kg) concurrently with CCl4 for 2 weeks resulted in 13.6% and 21.5% reduction in serum creatinine and increase in the level of depleted reduced glutathione (23.1% and 31.8%), respectively, when compared with the positive control group. Chitosan nanoparticles (20 mg/kg) revealed a significant (p ˂ 0.05) decrease in malondialdehyde levels (30.6%), tumour necrosis factor-α (33.6%), interleukin-1ß (31.1%), and caspase-3 (36.6%). CONCLUSIONS: Chitosan nanoparticles afforded significant protection and amelioration against CCl4-induced nephrotoxicity. Thus, chitosan nanoparticles could afford a potential nanotherapeutic system for the management of nephrotoxicity which allows for broadening their role in biomedical delivery applications.


Assuntos
Quitosana , Nanopartículas , Animais , Ratos , Quitosana/química , Ratos Wistar , Tetracloreto de Carbono/toxicidade , Tamanho da Partícula
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